Downregulation of miR-200a-3p induced by hepatitis B Virus X (HBx) Protein promotes cell proliferation and invasion in HBV-infection-associated hepatocarcinoma

Abstract

BackgroundHepatitis B Virus X (HBx) Protein encoded by HBV is believed to be the major player in the process of HBV-induced oncogenesis. Ectopic expression of miR-200a-3p was reported to be associated with diverse tumorigenesis. This study aimed to better understand the role of miR-200a-3p and its correlation with HBx in HBV-induced hepatocellular carcinoma (HCC). MethodsIn this report, we examined the gene expression using quantitative RT-PCR and protein expression using Western blotting analysis. Cells were transfected with miR-200a-3p mimics or empty vector, and HBx-carrying vector or empty vector. Cell viability was tested using CCK-8 assay. Wound healing assay was performed to assess cell migration while Transwell assay was performed to evaluate cell invasion. ResultsmiR-200a-3p was downregulated in HBV-positive tissue samples compared with HBV-negative tissue samples. This result was further confirmed with HBV-positive and – negative cell lines. HBx protein was overexpressed in HBV-positive cells where expression of miR-200a-3p was significantly suppressed. Increased cell viability, altered cell cycle progression, increased cell migration and invasion occurred in HBx-overexpressed cells compared to its controls. In forced expressed miR-200a-3p cells, cell viability, cell migration and invasion were significantly decreased, and cell cycle status was altered compared to its controls. ConclusionsTaken together, pathogenetic function of HBx is negatively correlated with miR-200a-3p in HBV-cased HCC through regulating cell viability, cell cycle arrest, cell migration and cell invasion.